5(6)-Benzene ring substituted benzimidazole-2-carbamate derivatives having anthelmintic activity

ABSTRACT

R7 is lower alkyl having 1 to 4 carbon atoms or aryl, and n is 1-4; R2 is lower alkyl having from 1 to 6 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, lower alkenyl or lower alkynyl having 3 to 6 carbon atoms, or aralkyl or aryl; R5 is lower alkenyl, lower alkynyl, or aralkyl; and the R1 substitution is at the 5(6)-position. These compounds are useful as pesticides, particularly as anthelmintic and antifungal agents.   WHERE R is a lower alkyl group having 1 to 4 carbon atoms; R1 is SOR2, -SO2R2, -SCN, -SR5, -OR5 or M&#39;&#39;(CH2)nMR7 where M and M&#39;&#39; are independently   This application describes further species embraced by the following generic formula:

United States Patent 1 Beard et al.

[ Dec. 30, 1975 [54] 5(6)-BENZENE RING SUBSTITUTEDBENZIMIDAZOLE-Z-CARBAMATE DERIVATIVES HAVING ANTHELMINTIC ACTIVITY [75]Inventors: Colin C. Beard, Palo Alto; John A.

Edwards, Los Altos; John H. Fried, Palo Alto, all of Calif.

[73] Assignee: Syntex (U.S.A.) Inc., Palo Alto,

Calif.

[22] Filed: Nov. 25, 1974 [21] Appl. No.: 526,861

Related US. Application Data [63] Continuation-in-part of Ser. No.417,963, Nov. 21, 1973, which is a continuation-in-part of Ser. No.319,299, Dec. 29, 1972, abandoned.

[52] US. Cl 260/309.2; 260/454; 260/562 R;

260/462 A; 260/575; 260/578; 424/273 [51] Int. Cl. C07D 235/32 [58]Field of Search 260/309.2

[56] References Cited UNITED STATES PATENTS 3,574,845 4/1971 Actor26013092 3,694,455 9/1972 Dunn ..260/309.2

FOREIGN PATENTS OR APPLICATIONS 1,114,069 5/1968 United Kingdom260/309.2

Primary Examiner-Natalie Trousof Attorney, Agent, or Firm-Joseph I.Hirsch; William B. Walker [57] ABSTRACT This application describesfurther species embraced by the following generic formula:

H c rl-coorz where R is a lower alkyl group having 1 to 4 carbon atoms;R? is SOR -SO R SCN, SR OR or M(CH ),,MR where M and M are independently9 Claims, No Drawings 5(6)-BENZENE RING SUBSTITUTEDBENZIMIDAZOLE-Z-CARBAMATE DERIVATIVES HAVING ANTHELMINTIC ACTIVITYREFERENCE TO PARENT APPLICATION This application is acontinuation-in-part application of application Ser. No. 417,963, filedNov. 21, 1973, which, in turn, is a continuation-in-part application ofapplication Ser. No. 319,299, filed Dec. 29, 1972, now

abandoned.

FIELD OF THE INVENTION This invention relates to novel-chemicalcompounds. More particularly, this invention relates to novelanthelmintically active benzimidazole-2-carbamate derivatives whereinthe benzene ring is substituted at the (6)-position.

BACKGROUND OF THE INVENTION 4 H R1 c i i-C0012 i 7 H (I) where R is alower alkyl group having 1 to 4 carbon atoms; R is SOR SO R SCN, SR', ORor M'(Cl-1 ),,MR where M and M are independently R is lower alkyl having1 to 4 carbon atoms or aryl, and n is 14; R is a lower alkyl having from1 to 6 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, loweralkenyl or lower alkynyl having 3 to 6 carbon atoms, or aralkyl or aryl;R is lower alkenyl, lower alkynyl or aralkyl; and the R substitution isat the 5(6)-position.

As stated therein, the term lower alkyl referred to both straight andbranched chain alkyl groups having either a total of from 1 through 4carbon atoms or from 1 through 6 carbon atoms, and thus includedprimary, secondary and tertiary alkyl groups. Typical lower alkylsincluded, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl,isobutyl, t-butyl, n-amyl, n-hexyl and the like. The term cycloalkylreferred to cyclic hydrocarbon groups having from 3-to 7 carbon atomssuch as, for example, cyclopropyl, cyclopentyl, cyclohexyl, and thelike. The term lower alkenyl referred to an unsaturated hydrocarbongroup having from 3 to 6 carbon atoms and a single carbon-carbon doublebond, provided that the double bond was not on the a-carbon atom.Typical alkenyl groups included, for

example, 2-propenyl, Z-butenyl, 3-butenyl, and the like. The term loweralkynyl referred to an unsaturated'hydrocarbon group having from 3 to 6carbon atoms, and a single carbon-carbon triple bond, provided also thatthe triple bond was not on the a-carbon atom. Typical alkynyl groupsincluded, forexample, 2-propynyl, 2-butynyl, 3-butynyl, and the like. Itwas stated that an alkyl, alkenyl or alkynyl group of the R moiety couldbe optionally substituted with one or more radicals, for example,thiocyanato; alkoxy, such as methoxyl; aryl, such as phenyl; aroyl, suchas benzoyl; hydroxy; cycloalkyl; halo; cyano; or nitro radicals. Theterm alkoxy referred to the group having the formula RO- wherein R is alower alkyl as defined above. Typical alkoxy groups included, forexample, methoxy, ethoxy, t-butoxy and the like. The term halo referredto iodo, bromo, chloro and fluoro groups. The term aryl referred to anaromatic hydrocarbon group, such as phenyl. The term aralkyl" referredto an aryl substituted alkyl group, such as, for example, benzyl orphenethyl. The term aroyl" referred to the group having the formulawhere R is an aryl group. The aryl or aralkyl groups could be optionallysubstituted with one or more lower alkyl, alkoxy, halo, nitro, cyano,thiocyanato, isothiocyanato, trifluoromethyl, alkylthio, alkylsulfinyl,a1- kysulfonyl, acyl or acylaminov where the acyl portion has 1 to 6carbon atoms, SO NR R or N(R )SO R radicals; where R and R areindependently hydrogen or lower alkyl having 1 to 6 carbon atoms. Theterms alkylthio, alkylsu1finy1", and alkylsulfonyl referred to thosegroups having the formula respectively, where R is a lower alkyl (1-6c)as defined above. The term acyl" referred to acyl groups derived fromcarboxylic acids having 1 through 6 carbon atoms such as acetyl,propionyl, butyryl, valeryl, isovaleryl, hexanoyl and the like.

SUMMARY OF THE INVENTION This application describes further compoundsembraced by formula 1 above. They are as follows:

5(6)-(3-chloropropy1sulfinyl)-2-carbomethoxyaminobenzimidazole;

5( 6 3 -bromopropylsulfinyl )-2 -carbomethoxyaminobenzimidazole;

5(6)-(3-hydroxypropylsulfiny1)-2-carbomethoxyaminobenzimidazole;

5(6)-(2,2-dichloroethylsulfinyl)-2-carbomethoxyaminobenzimidazole;

5 6 3 -phenyl-prop-2-en-1-ylthio)-2-carbomethoxyaminobenzimidazole;

5(6)-(3-phenyl-prop-2-en-1-y1sulfinyl)-2-carbomethoxyaminobenzimidazole;

5(6)-(3-chloro-prop-2-en-1-ylthio)-2-carbomethoxyaminobenzimidazole;

l-(n-butylisocyanate )-5(6)-(but-3-en-.l ylthio) 2=carbomethoxyaminobenzimidazole;- and l-(n-butylisocyanate)-56)-(4-chlorophenoxyethoxy)2carbomethoxyaminobenzimidazole; and thecorresponding Z-carbethoxyamino, 2-carbopropoxyamino and2-carbobutoxyamino compounds.

Of these compounds,5(6)-benzyloxyethoxy-2-carbomethoxyaminobenzimidazole,5(6)-(3-chloroprop- 2-3nl yl-thio )2carbomethoxyaminobenzimidazole,5(6)(but-3-en-lylthio)2-carbomethoxyaminobenzimidazole,5(6)-(p-methylphenoxyethoxy-2carbomethoxyaminobenzimidazole,5(6)-(p-chlorophenoxyethoxy)-2carbomethoxyaminobenzimidazole,5(6)-(pmethoxyphenoxyethoxy)2-carbomethoxyaminobenzimidazole, 5 (63-chloroprol -ylsulfinyl)-2-carbomethoxyaminobenzimidazole, particularly5(6)-(pchlorophenoxyethoxy)2-carbomethoxyaminobenzimidazole,5(6)-benzyloxyethoxy-2-carb0methoxyaminobenzimidazole,5(6)-(3-chloroprop-l-ylsulfinyl)-2carbomethoxyaminobenzimidazole and5(6)- (but-3-en- 1 ylthio)2-carbomethoxyaminobenzimidazole are presentlypreferred because they have shown substantial activity against thehelminths specifically referred to above.

Of particular interest are the compounds of the formula:

where R and n are as defined above, particularly where R is methyl and nis 2, and the phenyl ring of the 5(6)- substituent is optionallysubstituted with one or more halo, alkyl, alkoxy, alkylthio,alkylsulfinyl or alkylsulfonyl (as defined above) substituents, R ishydrogen or C(O)NHR; and R is aryl, aralkyl, or lower alkyl having 1 to12 carbon atoms and optionally substituted with a COOR group where R isas defined above. Exemplary compounds within the class of compounds ofFormula ll are 5(6)benzyloxyethoxy-Z-carbomethoxyaminobenzimidazole,5(6)-(4-chlorobenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole,5(6)-(4- bromobenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole,5(6)-(4-methylbenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole,5(6)-(4-methoxybenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole, 5( 6 2,4dichlorobenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole,5(6)-(3,4-dichlorobenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole,5(6)-(4- methylthiobenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole,5(6)-(4-methylsulfinylbenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole,5(6)-(4methylsulfonylbenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole,5(6)-(4-chloro-3-methylbenzyloxyethoxy)-2carbomethoxyaminobenzimidazole,and 5(6)-(2,4,6-trichlorobenzyloxyethoxy)2-carbomethoxyaminobenzimidazole.

Also of particular interest are the compounds of the' formula:

H 0 (CH O /C NCOOR l R (In) where R and n are as defined above,particularly where R is methyl and n is 2, and the phenyl ring of the5(6)- substituent is substituted with one or more halo, alkyl, alkoxy,alkylthio, alkylsulfinyl or alkylsulfonyl (as defined above)substituents, R is hydrogen or C- (O)Nl-lR and R is aryl, aralkyl, orlower alkyl having 1 to 12 carbon atoms and optionally substituted witha COOR group where R is as defined above. Exemplary compounds within theclass of Formula [II compounds are5(6)-(4-chlorophenoxyethoxy)-'2-carbomethoxyaminobenzimidazole, 5 64-bromophenoxyethoxy)-2carbomethoxyaminobenzimidazole; 5(6)-(4-methylphenoxyethoxy)2-carbomethoxyaminobenzimidazole,5(6)-(4-methoxyphenoxyethoxy)-2-carbomethoxyaminobenzirnidazole,5(6)-(2,4-dichlorophenoxyethoxy)-2-carbomethoxyarninobenzimidazole,5(6)-(3,4-dichlorophenoxyethoxy)-2-carbomethoxyaminobenzimidazole,5(6)-(4-methylthiophenoxyethoxy)-2-carbomethoxyaminobenzimidazole,'5(6)-(4- methylsulfinylphenoxyethoxy)-2-carbomethoxyaminobenzimidazole,5(6)-(4-methylsulfonylphenoxyethoxy)-2carbomethoxyaminobenzimidazole,5(6)- (4-chloro-3methylphenoxyethoxy)-2-carbomethoxyaminobenzimidazole,and 5(6)-(2,4,6-trichlorophenoxyethoxy)2-carbomethoxyaminobenzimidaozle.

Stronglyoides, and specifically, for example against Nematospiroidesdubius, Hymenolepis Nana, Syphacia obvelata, and/or Aspiculuristetraptera. In particular, these compounds are found to exhibit highactivity against various helminthic infections of the intestinal tractof economically important animals, coupled with low systemic toxicity tothe host animal.

The compounds of the present invention are also useful as antifungalagents, particularly as systemic fungicides for controlling fungaldiseases of plants of economic importance.

In addition to the stated anthelmintic and antifungal properties,certain compounds of the present invention are also useful asintermediates in the preparation of further compounds of this invention.For example, the 5(6)-substitutedthio compounds be prepared and thenutilized as starting materials for the preparation of the corresponding5(6)-substitutedsulfinyl compounds.

Where the compound has a basic moiety, the term nontoxic salts as usedherein refers to those pharmaceutically acceptable salts of thecompounds of this invention which do not adversely affect the antifungalor anthelmintic properties of the basic compounds, such as those saltsconventionally used in the art. Such non-toxic salts include, forexample, salts of inorganic acids such as, for example, sulfuric,sulfonic, sulfamic, nitric, phosphoric, hydrochloric acids and the like,and salts of organic acids such as, for example, acetic, citric, lactic,palmitic, tartartic, succinic. maleic, benzoic acids and the like. Wherethe compound has an acidic 7 moiety, the non-toxic salts include cationsalts, such as, for example, the salts of sodium, potassium, ammonium,and the like.

The amount of the compound to be administered will depend upon theactual compound utilized, and upon the weight of the animal beingtreated. In general, however, the daily dosage level will usually bebetween about 5 mg/kg or less and 100 mg/kg of body weight of the animalbeing treated. The active ingredient is adapted to be administered tothe animal by mixing it with the diet of the animal, as with a feed mix,or formulating it with a non-toxic carrier to give anthelminticcompositions. The carrier may be an orally ingestible container for theactive ingredient such as, for example, a gelatin capsule, or it may bean excipient of the kind normally used in medicaments of this character,including maize starch, terra alba, lactose, sucrose, calcium phosphate,gelatin, stearic acid, agar, pectin or the like. Examples of suitableliquid carriers are peanut oil, sesame oil and water.

A wide variety of pharmaceutical forms can be employed in those caseswherein the medicament is not admixed with the feed. Thus, if a solidcarrier is used, the compound can be administered in tablet or capsuleform. If a liquid carrier is used, the medicament may be in the form ofa soft gelatin capsule or in a liquid suspension.

The compounds of this invention can be prepared according to theprocedures set forth in aforementioned applications Ser. Nos. 319,299and 417,963, the entire disclosures of which (particularly thoseportions thereof relating to the methods of chemical preparations) areincorporated herein by reference.

DESCRIPTION OF SPECIFIC EMBODIMENTS The following specific descriptionis given to enable those skilled in this art to more clearly understandand practice the present invention. It should not be considered as alimitation upon the scope of the invention but merely as beingillustrative and representative thereof.

Unless otherwise indicated, all temperatures are in degrees centrigradeand all percentages are by weight.

PREPARATION l 175G. of S-methyl isothiouronium sulfate in one liter ofwater is cooled to C and 162.5 g. of methylchloroformate added, followedby the addition of a solution of 250 g. potassium hydroxide in 750 ml.water at O to C. The crude product is extracted into benzene, thebenzene dried and evaporated, and the residue recrystallized frommethanol. l,3-bis(methoxycarbonyl)-S- methyl isothiourea is thusobtained.

In a similar manner, substituting ethylchloroformate,propylchloroformate and butylchloroformate for the methylchloroformate,l,3-bis(ethoxycarbonyl )-S- methyl isothiourea, l,3-bis(propoxycarbonyl)-S- methyl isothiourea, and l,3-bis(butoxycarbonyl)-S- methylisothiourea are, respectively, prepared.

EXAMPLE 1 6 G. of 2-nitro-4-thiocyanatonaniline in 30 ml. ofdimethylformamide is treated under nitrogen with 1.2 g. of sodiumborohydride at 20 to 30. After 1 /2 hours ml. of acetone is added,followed 2 hours later by 10 g. of 3-chloropropylbromide. The mixture isleft at -25 for 16 hours, then diluted with water. The oily product isextracted into chloroform and passed 8 through a silica column.2-Nitro-4-(3chloropropylthio)aniline is isolated by evaporation of thesolvent.

6 G. of 2-nitro-4-(3-chloropropylthio)aniline is treated in m. ofethanol and 120 ml. of water with 30 g. of sodium hydrosulfite (N21 S Oon the steam bath for about Sminutes. The reaction mixture isconcentreated under vacuum and extracted well with chloroform.Evaporation of the dried extract affords 1,2-diamino-4-(3-chloroprophylthio)benzene.

4G. of l,2-diamino-4-(3-chlorophropylthio)benzene and 4.2 g. ofl,3-bis(methoxycarbonyl)-S-metyl isothiourea are heated in a mixture of40 ml. of ethanol, 40 ml. of water and 1.5 ml. of acetic acid for 4hours at reflux. The mixture is cooled and 5(6)-(? -chloropropylthio)-2-carbomethoxyaminobenzimidazole filtered off.Recrystallization may be effected from methanol chloroform (mp. 201.5202.5).

1.5 G. of 5(6)-(3-chloropropylthio)-2-carbomethoxyaminobenzimidazole isdissolved in 100 ml. of chloroform and 10 ml. of acetic acid at 20. Asolution of 1.05 g. of m-chloroperbenzoic acid in 30 ml. of chloroformis added and the mixture allowed to warm slowly to 20-25. After 3 hoursat 2025 the mixture is concentrated under vacuum and the residue treatedwith sodium bicarbonate solution. The crude product is filtered off andrecrystallized from methanol to afford5(6-(3-chloropropylsulfinyl)-2-carbomethoxyaminobenzimidazole (m.p. 206dec.).

EXAMPLES 2 and 3 The procedure of Example 1 is repeated substituting1,2,3-trichloropropene for the 3-chloropropyl bromide to afford5(6)-(2,3-dichloroprop-2-en-l-ylthio)-2-carbomethoxyaminobenzimidazole(m.p. 182 dec.) and 5(6)-(2,3-dichloroprop-2-en-l-ylsulfinyl)-2-carbomethoxyaminobenzimidazole (m.p. -270 dec.).

EXAMPLES 4 and 5 The procedure of Example 1 is repeated substituting4-bromobut-l-ene for the 3-chloropropyl bromide to afford5(6)-(but-3-en-l-ylthio)-2-carbomethoxyaminobenzimidazole (m.p. -200dec.) and 5 (6)-(but-3-en-l-ylsulfinyl)-2-carbomethoxyaminobenzimidazole (m.p. -230dec.).

EXAMPLES 6 and 7 The procedure of Example 1 is repeated substituting 2-(t-butoxy)ethyl bromide for the 3-chloropropyl bromide to afford5(6)-(t-butoxyethylthio)-2-carbomethoxyaminobenzimidazole (m.p. l75l 79and 5(6)- (t-butoxyethylsulfinyl)-2-carbomethoxyaminobenzimidazole (m.p.156 dec.).

EXAMPLE'S 8 and 9 The procedure of Example l is repeated substituting2-benzyloxyethyl-methane sulfonate (prepared in pyridine from2-benzyloxyethanol and methanesulfonyl chloride) for the 3-chloropropylbromide to afford5(6)-benzyloxyethylthio-2-carbomethoxyaminobenzimidazole (m.p. 182dec.). and 5(6)-benzyloxyethylsulfinyl)-2-carbomethoxyaminobenzimidazole(m.p. dec.

EXAMPLES l0 14 The procedure of Example 1 is repeated substituting2,2-bismethoxyethyl bromide, 3-bromopropanol, l ,l ,Z-trichloroethane,l-bromo-3-methoxypropane, and l-bromo-4-phenoxybutane for the3-chl0ropropyl 9 bromide to afford, respectively,(6)-(2,2-dimethoxyethylsulfinyl)-2-carbomethoxyaminobenzimidazole (m.p.-l52 dec.), 5(6)-(2-hydroxypropylsulfinyl)-2-carbomethoxyaminobenzimidazole (m.p. -203 dec.),5(6)-(2,Z-dichloroethylsulfinyl)-2-carbomethoxyaminobenzimidazole (m.p.210 dec.), 5(6)-(3-methoxypropylsulfinyl)-2-carbomethoxyaminobenzimidazole (m.p. 170 dec.),and 5(6)-phenoxybutylthio-2-carbomethoxyaminobenzimidazole (m.p. l89-l9ldec.).

EXAMPLE 15 A solution of 7.5 g. of 2-benzyloxyethanol in 30 ml. ofdimethylformamide is treated with 1.2 g. of sodium hydride. When themixture is homogeneous, 3.5 g. of 2-amino-4-chloro-l-nitrobenzene isadded and mixture heated at 1 l0l20 for 4 hours. The mixture is cooled,diluted with water and extracted with benzene. The crude product istreated with charcoal and isolated by precipitation with cyclohexane toafford Z-amino-lnitro-4-(2-benzyloxyethoxy)benzene.

1.6 G. of 2-amino-4-(2-benzyloxyethoxy)-1-nitrobenzene is treated in 100ml. of methanol and 50 ml. of water with g. of sodium hydrosulfite (Na SO on the steam bath for minutes. The reaction mixture is concentratedunder vacuum and extracted with chloroform. Evaporation of the extractaffords 1,2-diamino-4- (2-benzyloxyethoxy)-benzene.

1.4 G. of l,2-diamino-4-(2-benzyloxyethoxy)benzene and 1.4 g. ofl,3-bis(methoxycarbonyl)-S-methyl isothiourea is treated in ml. ofethanol and 20 ml. of water with 0.5 ml. of acetic acid. After refluxingfor 5 hours the mixture is cooled and filtered. Recrystallization of theproduct from methanol-chloroform affords5(6)-(2-benzyloxyethoxy)-2-carbomethoxyaminobenzimidazole (m.p. -l9ldec.).

EXAMPLE 16 The procedure of Example 15 is repeated substituting2-methylthioethanol for the Z-benzyloxyethoxy to afford5(6)-(Z-methylthioethoxy)-2-carbomethoxyaminobenzimidazole. This productis treated in accordance with the last paragraph of Example 1substituting peracetic acid (2 moles) for the m-chloroperbenzoic acid toafford 5(6)-(2-methylsulfonylethoxy)-2-carbomethoxyaminobenzimidazole(m.p. 225-226 dec.).

EXAMPLES l7 and 18 4.7 G. of 2-nitro-4-thiocyanatoacetanilide isdissolved in 30 ml. of dimethylformamide under nitrogen. 0.8 G. ofsodium borohydride is added at 2030. After 1 hour 10 ml. of acetone isadded and then after a further 2 hours, 2.7 g. of l,3-dichloropropene isadded. The mixture is left for 24 hours at 2025, then drowned intowater. 2-Nitro-4-(3-chloro-prop-2-en-1- ylthio)acetanilide is filteredoff and purified by passage, in chloroform solution, through a column ofsilica.

4.3 G. of the product of the preceding paragraph is treated at 20-25with 50 ml. of methanol containing 10 ml. of 5N aqueous sodiumhydroxide. After 1 hour 10 ml. of water is added followed by 20 g. ofsodium hydrosulfite. The mixture is warmed for about 5 minutes until theorange color is discharged and then stripped under vacuum and dilutedwith water. 1,2- diamino-4-(3-chloro-prop-2-en-l-yl-thio)benzene isisolated by chloroform extraction.

2.9 G. of the product of the preceding paragraph is treated with 3.3 g;of l,3-bis(methoxycarbonyl)-S- methyl isothiourea and 1.5 ml. of aceticacid in 30 ml. of ethanol and 30 ml. of water on the steam bath for 4hours. The mixture is cooled and filtered. Recrystallization frommethanol affords 5(6)-(3-chl0roprop-2-en lylthio)-2-carbomethoxyaminobenzimidazole (m.p. -202 dec.). 7

The product of the preceding paragraph is treated in accordance with theprocedure of the last paragraph of Example 1 to afford 5(6)-(3-chloro-prop-2-en-l-ylsulfinyl)-2-carbomethoxyaminobenzimidazole(m.p. 240 dec.).

EXAMPLES 19 and 20 The procedure of Examples 17 and 18 is repeatedsubstituting 3-phenoxypropyl bromide for the 1,3- dichloropropane toafford 5(6)-(3-phenoxypropylthio)-2-carbomethoxyaminobenzimidazole (m.p.196 dec.) and5(6)-(3-phenoxypropylsulfinyl)-2-carbomethoxyaminobenzimidazole (m.p.189 dec.).

EXAMPLES 21 and 22 The procedure of Examples 17 and 18 is repeatedsubstituting 2,3-dichloropropene for the l,3-dichloropropene to afford5(6)-(2-chloro-prop-2-en-1?ylthio)- 2-carbomethoxyaminobenzimidazole(m.p. -21 1 dec.) and5(6)-(2-chloroprop-2-en-1-ylsulfinyl)-2-carbomethoxyaminobenzimidazolem.p. -l 18 dec.).

EXAMPLE 23 The procedure of Example 17 is repeated except2-(phenylthio)ethyl chloride is substituted for the 1,3- dichloropropeneto afford 5(6)-[2-(phenylthio)ethylthio]-2-carbomethoxyaminobenzimidazole (m.p.210- 212).

EXAMPLE 24 The procedure of the first paragraph of Example 17 isrepeated substituting 2-(phenylsulfinyl)ethyl chloride [prepared bytreating 2-(phenylthio)ethyl chloride with peracetic acid]f0r thel,3-dichloropropene to afford l-acetamide-2-nitro-4-[2-(phenylsulfinyl)ethylthio]benzene.

5 G. of the product of the preceding paragraph is treated at 20-25 with50 ml. of methanol containing 10 ml. of 5N aqueous sodium hydroxide.After 1 hour 250 ml. of methanol and 50 ml. of water with 3 g. offerrous sulfate and 25 g. of iron powder (activated with 1 ml. ofhydrochloric acid) are added and held at reflux for 18 hours After theiron residue is filtered off, the filtrate is concentrated under vacuumto afford 1,2- diamino-4-[2-(phenylsulfinyl)ethylthio]benzene.

The product of the preceding paragraph is treated in accordance with thethird paragraph of Example 17 to afford5(6)-[2-(phenylsulfinyl)ethylthio]-2-carbomethoxyaminobenzimdazole (m.p.l86-l 88).

EXAMPLE 25 The procedure of the first paragrpah of Example 17 isrepeated substituting 2-(ethylsulfinyl)ethyl bromide [prepared bytreating 2-(ethylthio)ethyl bromide with peracetic acidlfor thel,3-dichloropropene to afford l-acetamido-2-nitro-4-[ Z-(ethylsulfinyl)ethylthio]benzene. This product is treated in accordance with thesecond and third paragraphs of Example 24 to afford5(6)-[2-(ethylsulfinyl)ethylthio]-2-carbomethoxyaminobenzimidazole (m.p.-l90 dec.).

EXAMPLE 26 A mixture of4.1 g. of 2-nitro-4-hydroxy-acetanilide, 4.7 g.of 3-phenoxypropylbromide and 3.1 g. of potassium carbonate in .100 ml.of acetone is treated under reflux for 16 hours. The mixture is dilutedwith water and the 2-nitro-4-(2-phenoxypropoxy)acetanilide is filteredoff.

The product of the preceding paragraph is treated in accordance with thesecond and third paragraphs of Example 17 to afford 5(6)-(3-phenoxypropoxy)-2-car- .bornethoxyaminobenzimidazole (m.p. -220dec.).

EXAMPLE 2729 EXAMPLE 3 The(6)-[2-(ethylthio)ethoxy]-2-carbomethoxyaminobenzimidazole of Example 27is treated in accordance with the last paragraph of Example 1 to afford5 (6)-[Z-(ethylsulfinyl)ethoxy]-2-carbomethoxyaminobenzimidazole (m.p.212 dec.).

EXAMPLES 31 and 32 3.45 G. of 2-amino-4-chloro-l-nitrobenzene and 5.3 g.of sodium sulfide rnonohydrate in 30 ml. of dimethylformamide is heatedat about 100 for 1 hour under nitrogen, cooled and 4.5 g. of3-phenylpropyl bromide added, held at 20".--25 for 4 hours, then dilutedwith water. The product is filtered off and recrystallized from methanolto afford 2-amino-4-(3-phenylpropylthio)-l-nitrobenzene.

3.5 G. of the product of the preceding paragraph and 3.5 g. 'of ironpowder in 100 ml. of toluene, 3.5 ml. of water and 0.2 ml. ofconcentrated hydrochloric acid is refluxed for 2 hours, cooled, filteredand the filtrate evaporated to afford1,2-diamino-4-(3-pheny1propylthio)benzene. This product is treated inaccordance with the third and fourth paragraphs of Example 1 to afford5(6)-(3-phenylpropylthio)-2-carbomethoxyaminobenzimidazole (m.p. 18l185)and 5(6)-(3- phenylpropylsulfinyl )-2-carbomethoxyaminobenzimidazole(m.p. -207 dec.).

EXAMPLES 33 and 34 EXAMPLE 35 A mixture of 4.6g. of2-nitro-4-acetoxy-acetanilide and 5.6 g. of potassium carbonate in 150ml. of methanol is refluxed for 5 minutes and then' 12 g. of2-phenylthioethylmethanesulfonate (prepared from Z-phenylthioethanol inpyridine" with meth'anesulfonyl' chloride and isolated from acidifiedwater by ether extraction) is added. The mixture is refluxed for 16hours then 10 ml. of water is added and the solute concentrated fromabout 1 hour. Water is added and the product filtered off and washedwith water and hexane to afford 2-nitro-4-[Z-(phenylthio)ethoxy]ani1ine.

2.8 G. of the product of the preceding paragraph is treated in ml. ofmethanol and 25 ml. of water with 15 g. of sodium hydrosulfite on thesteam bath for about 10 minutes. The mixture is concentrated undervacuum, diluted with water and extracted into chloroform. Evaporation ofthe dried extract affords 1,2- diamino-4-[2-(phenylthio)ethoxy]benzene.

1.8 G. of the product of the preceding paragraph is treated with 2 g. of1,3-bis(methoxycarbonyl)-S-methy1 isothiourea and 1 ml. of acetic acidin 25 ml. of ethanol and 25 ml. of water on the steam bath for 6 hours.The mixture is cooled and the product filtered off. Recrystallizationfrom methanol-chloroform affords 5(6)-[2-(phenylthio)ethoxy]-2-carbomethoxyaminobenzimidazole (m.p. 210 dec.).

EXAMPLE 36 The procedure of Example 35 is repeated substituting2-pheny1ethy1 bromide for the 2-phenylthioethyl methanesulfonate toafford 5(6)-(2-pheny1ethoxy)-2- carbomethoxyaminobenzimidazole (m.p. 222dec.).

EXAMPLES 3739 2 G. of 4-(2-bromoethoxy)-2-nitroacetanilide in 40 ml. ofacetone containing 0.95 g. of potassium carbonate is treated with 0.75g. of p-cresol. This mixture is stirred overnight at reflux, thencooled, filtered and the solvent removed by vacuum distillation to give4-[2-(pmethylphenoxy)ethoxy]-2-nitroacetanilide as a yellow gum. Thismay be used without purification or can be recrystallized from methanol.

2 G. of 4-[2-(p-methylphenoxy)ethoxy]-2- nitroacetanilide in 10 ml. ofmethanol is treated with 4 ml. of 5H NaOH solution. The mixture isheated for 20 minutes, then cooled and diluted with water. Theprecipitated 4-[Z-(p-methylphenoxy)ethoxy]-2-nitroaniline is collected,washed well with water and dried.

1.6 G. of 4-[2-(p-methylphenoxy)ethoxy1-2-nitroaniline in 20 ml. ofmethanol containing 0.5 g. of 5% palladized charcoal is hydrogenated at1 atmosphere pressure until the theoretical uptake of hydrogen hasoccurred. The catalyst is removed by filtration and the filtrateevaporated. The residual gum is treated with 1 .8 g. ofl,3-bis(meth0xycarbony1)-S-methyl isothiourea and 0.4 ml. of acetic acidin a boiling mixture of 10 ml. of ethanol and 10 m1. of water. After 3hours the mixture is cooled, filtered and5(6)-[2-(p-methy1phenoxy)ethoxy]-2-carbomethoxyaminobenzimidazole isrecrystallized from a mixture of methanol benzimidazole isrecrystallized from a mixture of methanol and chloroform (m.p. 2l02l2dec.).

In a similar manner, substituting p-methoxyphenol and p-chlorophenol forthe p-crcsol,5(6)-[2-(pmethoxyphenoxy)ethoxy1-2-carbomethoxyaminobenzimidazole (m.p.20821 1 dec.). and5(6)-[2-(pchlorophenoxy)ethoxy]-2-carbomethoxyaminobcnzimidazole (m.p.205-207 dec.) are prepared.

EXAMPLE 40 The procedure of the first paragraph of Example 26 isrepeated substituting 4-pherioxybuty1 bromide for the 3-phenoxypropylbromide to afford 2-nitro-4-(4- 13 phenoxybutoxy)acetanilide. Aftertreatment at 20-25 with methanolic-SN aqueous sodium hydroxide, 1.2 g.of the resultant 2-nitro-4-(4-phenoxybutoxy)ani1ine in a mixture of 20ml. of methanol and 0.3 g. of palladized charcoal is hydrogenated underambient conditions. When the theoretical amount of hydrogen has beentaken up, the mixture is filtered and the filtrate stripped to affordl,2-diamino-4-(4-phenoxybutoxy)- benzene as a gum.

The procedure of the last paragragh of Example is repeated to afford5(6)-(4-phenoxybutoxy)-2-carbomethoxyaminobenizmidazole (m.p. l90-l93dec.

EXAMPLE 41 The procedure of Example 40 is repeated substitut ingcinnamyl bromide for the 4-phenoxybutyl bromide to afford5(6)-(3-phenyl-prop-2-en-1-yloxy)-2-carbomethoxyaminobenzimidazole (m.p.2152l 8 dec.

EXAMPLE 42 The procedure of the first paragraph of Example 15, thecatalytic reduction of the first paragraph of Example 41, and the thirdparagraph of Example 15 are repeated substituting2-(2-methoxyethoxy)ethanol for the 2-benzyloxyethanol to afford5(6)-[2-(2'-methoxyethoxy)ethoxy]-2-carbomethoxyaminobenzimidazole (m.p.184185 dec.).

EXAMPLE 43 5.85 G. of 1-amino-2-nitro-4-thiocyanatobenzene in ml.dimethylformamide is treated under nitrogen with 1.14 g. sodiumborohydride at not greater than 30. The mixture is stirred for 1 hour at1520, then treated with 12 g. of 1,3-dibromopropane at 2025. After afurther 3 hours, water is added and the crude product extracted withchloroform. The dried chloroform solution is passed through a column ofsilica gel to remove polar material. Pure 1-amino-2-nitro-4-(3-bromopropylthio)benzene is obtained from the eluate.

3.0 G. of l-amino-2-nitro-4-(3-bromopropylthio benzene in 18 ml.concentrated hydrochloric acid is treated with a solution of 10 g.stannous chloride. The mixture is cooled to about 30, the product isfiltered off and washed with 10 ml. of 6N hydrochloric acid. The productis dissolved in 30 ml. of water and treated with potassium acetate to pHof 3-4, then added to ml. of ethanol. 3 G. of l,3-bis-methoxycarbonyl-S-methyl isothiourea is added and the reaction mixture is held at refluxfor 3 hours. The mixture is cooled and5(6)-(3-bromopropylthio)-2-carbomethoxyaminobenzimidazole isolated byfiltration. Recrystallization may be effected from methanol-chloroform(m.p. 185 dec.).

0.7 G. of 5(6)-(3-bromopropylthio)-2-carbomethoxyaminobenzimidazole isdissolved in a mixture of 2 ml. acetic acid and 50 ml. chloroform. Asolution of 0.42 g. m-chloroperbenzoic acid in 20 ml. chloroform isadded at 20 to 1 5. The mixture is allowed to warm slowly to 20 and leftfor 5 hours. The solvents are removed under vacuum and the residuetreated with sodium bicarbonate solution.5(6)-(3-bromopropylsulfinyl)-2- carbomethoxyaminobenzimidazole -isfiltered off, and may be recrystallized from isopropanol (m.p. 169dec.).

EXAMPLE 44 5.85 G. of l-amino-2-nitro-4-thiocyanatobenzene is treated in20 ml. dimethylformamide under nitrogen at 20-25 with 1.14 g. sodiumborohydride. After 1 hour 10 ml. of methylthioethylchloride is added andthe mixture stirred overnight, diluted with water and extracted withchloroform. The dried chloroform solution is passed through a silica gelcolumn, then evaporated to dryness to afford1-amino-2-nitro-4-methylthioethylthiobenzene.

2.5 G. of 1-amino-2-nitro-4-methylthioethylthiobenzene in ml. methanoland 40 ml. water is treated at reflux for 5 hours with 1.25 g. ferroussulfate and 5 g. iron powder (the latter added in 2 portions). Themixture is filtered, stripped and the residual 1,2-diamino-4-methylthioethylthiobenzene extracted into chloroform, washed, dried andisolated by evaporation of the solvent.

1.8 G. 1,2-diamino-4-methylthioethylthiobenzene and 1.9 g.1,3-bis(methoxycarbonyl)-S-methyl isothiourea and 0.8 ml. acetic acid in20 m1. ethanol plus 20 ml. water are refluxed for 5 hours, cooled andfiltered. The product.5(6)-methylthioethylthio-2-carbomethoxyaminobenzimidazole, is purifiedby recrystallization from methanol-chloroform.

The product of the preceding paragraph is treated in accordance with thelast paragraph of Example 1 using peracetic acid instead ofm-chloroperbenzoic acid to afford5(6)-(2-methylthioethylsulfinyl)-2-carbomethoxyaminobenzimidazole,5(6)-(2-methylsulfinylethylthio) or a mixture thereof (m.p. 172 dec.).

EXAMPLE 45 The procedure of Example 44 is repeated substitutingethylthioethyl chloride for the methylthioethyl chloride and using twoequivalents of peracetic acid to afford5(6)-[2-(ethylsulfinyl)ethylsulfinyl]-2-carbomethoxyaminobenzimidazole(m.p. 169 dec.).

EXAMPLE 46 The procedure of Example 17 is repeated substitutingp-chlorophenylthiomethyl chloride for the 1,3- dichloropropene to afford5(6)-(p-chlorophenylthiomethylsulfinyl)-2-carbomethoxyaminobenzimidazole,5(6)-(p-chlorophenylsulfinylmethylthio)-2-carbomethoxyaminobenzimidazole,or a mixture thereof (m.p. -174 dec.).

EXAMPLES 47 and 48 The product of Examples 35 is oxidized in accordancewith the last paragraph of Example 1 with one equivalent ofm-chloroperbenzoic acid to afford 5(6)-[Z-(phenylsulfinyl)ethoxy]-2-carbomethoxyaminobenzimidazole (m.p. 230dec.), and with two equivalents of m-chloroperbenzoic acid to afford5(6)-[2-(phenylsulfonyl)ethoxy]-2-carbomethoxyaminobenzimidazole.

EXAM PLES 49-52 The procedure of Example 26 is repeated substitutingphenoxymethylchloride, benzyloxymethylchloride. phenylthiomethylchlorideand phenylsulfinylmethylchloride for the 3-phenoxypropylbromide toafford, respectively,5(6)-phenoxymethoxy-2-carbomcthoxyaminobenzimidazole,5(6)-benzyloxymethoxy-Z-carbomethoxyaminobenzimidazole,5(6)-phenylthiomethoxy-2-carbomethoxyaminobenzimidazole, and 5(6)-phenylsulfinylmethoxy-2-carbomethoxyaminobenzimidazole.

EXAMPLES 53-55 The procedure of Example 15 is repeated substituting2-(p-methylbenzyloxy)ethanol, 2-(p-chlorobenzyloxy)ethanol, and2-(p-methoxybenzyloxy)ethanol for the Z-benzyloxyethanol to afford,respectively,(6)-(p-methylbenzyloxyethoxy)-2-carbomethoxyaminobenzimidaozle,5(6)-(p-chlorobenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole, and5(6)-(pmethoxybenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole.

EXAMPLES 5659 EXAMPLES 60-63 The products of Examples 56-59 are oxidizedin accordance with the last paragraph of Example 1 to afford 5 6)-phenoxymethylsulfinyl-Z-carbomethoxyaminobenzimidazole,5(6)-benzyloxymethylsulfinyl- Z-carbomethoxyaminobenzimidazole,5(6)-diphenylmethoxyethylsulfinyl-2-carbomethoxyaminobenzimidazole, and5(6)-diphenylmethoxyethylsulfinyl-2- carbomethoxyaminobenzimidazole.

EXAMPLE 64 5(6)-Phenylthiomethylthio-2-carbomethoxyaminobenzimidazole ofExample 58 is treated with two equivalents of m-chloroperbenzoic acid inaccordance with the procedure of the last paragraph of Example l toafford 5(6)-phenylsulfinylmethylsulfinyl-2-carbomethoxyaminobenzimidazole.

EXAMPLE 65 The procedure of Example I is repeated substituting4-chlorobutylbromide for the 3-chloropropylbromide to afford5(6)-(4-chlorobutylsulfinyl)-2-carbomethoxyaminobenzimidazole.

EXAMPLES 66-68 The procedure of Example 37 is repeated substitutingp-methylthiophenol for the p-cresol to afford 5(6)-l2-(p-methylthiophenoxy)ethoxy]-2-carbomethoxyaminobenzimidazole. Thisproduct is treated with one or two equivalents of m-chloroperbenzoicacid to afford, respectively,5(6)-[2-(p-methylsulfinylphenoxy)ethoxy]-2-carbomethoxyaminobenzimidazoleand5(6)-[2-(p-methylsulfonylphenoxy)ethoxy]-2-carbomethoxyaminobenzimidazole.

EXAMPLES 69-71 The procedure of Example is repeated substituting2-(p-methylthiobenzyloxy)ethanol for the 2-benzyloxyethanol to afford5(6)-[2-(p-methylthiobenzyloxy)ethoxy]-2-carbomethoxyaminobenzimidazole.This product is treated with one or two equivalents ofm-chloroperbenzoic acid to afford, respectively, 5(6)-l2-(p-methylsulfinylbenzyloxy)ethoxy]-2-carbomcthoxyaminobenzimidazoleand 5(6)-[2-(p-methylsulfonylbenzyloxy )ethoxy-2-carbomethoxyaminobenzimidazole.

EXAMPLES 72-75 The compounds of Examples 1-71 can be reacted with asubstituted isocyanate of the formula OCNR where R" is aryl (e.g.,phenyl), aralkyl (e.g., benzyl) or lower alkyl having 1 to 12 carbonatoms optionally substituted with a -COOR group where R is a lower alkylhaving 1 to 4 carbon atoms, such as, for example, n-butylisocyanate, inan inert organic solvent, for example, tetrahydrofuran at about 0 toabout 40C for about /2 hour to about 96 hours to afford the corresponding l-substituted derivative thereof.

5(6)-(3-Chloropropylsulfinyl)-2-carbomethoxyaminobenzimidazole ofExample 1, 5(6)-(benzyloxyethoxy)-2-carbomethoxyaminobenzimidazole ofExample l5, 5(6)-(but-3-en-l-ylthio)-2-carbomethoxyaminobenzimdaozle ofExample 17, and5(6)-(pchlorophenoxyethoxy)-2-carbomethoxyaminobenzimidazole of Example39, are treated with nbutylisocyanate at 2025C for 24 hours, followed byconventional work-up, to afford, respectively,l-(nbutylisocyanate)-5-(6)-(3-chloropropylsulfinyl)-2carbomethoxyaminobenzimidazole,l-(nbutylisocyanate)-5(6)-(benzyloxyethoxy)-2-carbomethoxyaminobenzimidazole,l-( n-butylisocyanate 5 6 but-3-enl -ylthio)-2-carbomethoxyaminobenzimidazole, and1-(n-butylsiocyanate)-5(6)-(p-chlorophenoxyethoxy)-Z-carbomethoxyaminobenzimidazole.

By substituting l,3-bis(ethoxycarbonyl)-S-methyl isothiourea,l,3-bis(propoxycarbonyl)-S-methyl isothiourea, orl,3-bis(butoxycarbonyl)-S-methyl isothiourea for thel,3-bis(methoxycarbonyl)-S-methyl isothiourea used in the Examplesabove, the corresponding 2-carbalkoxyamino-5(6)-substitutedbenzimidazolecompounds can be prepared, where R is either ethyl, propyl or butyl.

In certain of the Examples above, specific reaction sequences have beenextended, in a general sense, to the preparation of other similar andrelated compounds. lt should be understood, however, that with respectto any compound which has been prepared by the extension of a specificreaction sequence, it may be necessary or desirable to utilize solvents,reaction media, recrystallization media, reaction times or temperatures,or amounts of materials, etc., other than the ones given in the specificreaction sequence upon which such extension is based. Additionally, thespecific reaction sequence or manner in which particular com pounds areto be prepared will depend, inter alia, upon the availability of thenecessary starting materials, or the ease in which the desired startingmaterials can be prepared, and the reactivity thereof. These variationsare deemed to be within the skill of those working in this art and willbe apparent from a consideration of the particular reactants utilizedand/or particular com pound desired to be produced.

EXAMPLE '76 Four young Swiss-Webster male mice l620 g.) are artificallyinfected with 200 larvae of the species Nematospiroides dubius(roundworm) and Hymenolepis nana (tapeworm) and naturally injected withl54() larvae of Syphacia uhvelata and Aspiculuris Ietraprtra (pinworms).The drug is administered in a commercial rat/mouse diet at the stateddose(s) from day 1 through day 18, the infection being introduced at Gay0. The

animals are sacrificed at day 18 and the parasites remaining in theentire small intestine, cecum and large bowel are counted anddifferentiated. The average number of each parasite remaining in eachmedicated 1 8 (6,)-(2,3-dichloro-prop-2-enl -ylsulfinyl)-2-carbomethoxyaminobenzimidazole; 5(6)-( 2-chloro-prop-2-en-l ylthio)-2-carbom ethoxyaminobenzimidazole;

. 5 group is compared to the average number remaining in 5(6) (2 chiorop en 1 ylsulfinyl) 2 carbome th t I d thoxyaminobenzimidazole;

e con ro is comparison is expresse as per5(6)-(but-3-en-l-ylthio)-2-carbomethoxyaminobenreduction over theparasites in the control group. The Zimidazole; data for illustrativecompounds of this invention is 5 3- 1 l lfi l) z arbomethoxtabulated inthe Table below. yaminobenzimi azole;

5( 6 )-R-2-carbomethoxyaminobenzimidazoles Test species R Ex. dose,*reduction) ppm Nd Hn So At 3-chloropropyll 125 100 0 lOO lOO sull'inyl62(3) 87.3 0 100 100 31(2) 59 0 100 W0 but-3-enl 4 l 100 0 100 100ylthio 62(2) 98.5 0 100 100 31 69 O 100 lOO 3-methoxypro- 13 125 100 O100 I00 pylsulfinyl 62 80 O 100 I00 2-(benzyloxy)- 15 125 95 100 100 I00ethoxy 62(2) 805 lOO 100 I00 31 O 73 100 100 3-chloroprop-2- 17 125 lOO0 100 100 en- 1 -ylthio 62 84 0 I00 100 prop-2-en-l-yl- 28 125 89 85 lOO100 oxy 62 7O 0 lOO 100 p-methylphen- 37 62 83 69 100 100 oxyethoxy 31 00 100 100 p-methoxyphen- 38 62 50 69 100 100 oxyethoxy 31 O O l O0 100p-chlorophen- 39 62 80 62 I00 100 oxyethoxy 31 61 50 100 100 NdNematospiroides dubius Hn Hymenolepis nana S0 Syphacia obvelata AtAspiculuris tetraptera The number in parenthesis refers to the number ofruns from which percent reductions are calculated and averaged to givethe data set forth for that particular dose in this Table.

While the present invention has been described with reference tospecific embodiments thereof, it should be understood by those skilledin this art that various changes may be made and equivalents may besubstituted without departing from the true spirit and scope of theinvention. In addition, many modifications may be made to adapt aparticular situation, material or composition of matter, process,process step or steps, or then-present objective to the spirit ofthisinvention without departing from its essential teachings.

What is claimed is:

l. A compound selected from the group consisting of:

5 6 3-chloropropylsulfinyl )-2-carbomethoxyaminobenzimidazole;

5 6 3-bromopropylsulfinyl )-2-carbomethoxyaminobenzimidazole;

5 6 3-hydroxypropylsulfinyl)-2-carbomethoxyaminobenzimidazole;

5 6 H 2,Z-dichloroethylsulfinyl )-2-carbomethoxyaminobenzimidazole;

5 6 3-phenyl-prop-2-enl -ylthio)-2-carbomethoxyaminobenzimidazole;5(6)-(3-phenyI-prop-2-en-l-ylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-(3-chloro-prop-2-en-l-ylthio)-2-carbomethoxyaminobenzimidazole;5(6)-(3-chloro-prop-2-en-l-ylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-(2,3-dichl0ro-pr0p-2-en-l-ylthio)-2-carbomethoxyaminobenzimidazole;

5 6 3-phenyl-prop-2-enl -yloxy )-2-carbomethoxyaminobenzimidazole;

5 6 )-phenylthioethoxy-Z-carbomethoxyaminobenzimidazole;

5 6 )-phenpropylthio-2-carbomethoxyaminobenzimidazole;

5(6)-phenpropylsulfinyl-2-carbomethoxyaminobenzimidazole;

5(6)-phenethoxy-2-carbomethoxyaminobenzimidazole;

5(6)-phenpropoxy-Z-carbomethoxyaminobenzimidazole;

5 (6 )-(prop-2-en-' l -'yloxy )-2-carbomethoxyaminobenzimidazole;

5 6 )-ethylsulfinylethylthio-2-carbomethoxyaminobenzimidazole;

5(6)-methylthioethylsulfinyl-Z-carbomethoxyaminobenzimidazole and5(6)-methylsulfinylethylthio-2-carbomethoxyaminobenzimidazole;

5(6)-cthylsulfinylethylsulfinyl-Z-carbomethoxyaminobenzimidazole;

5 6 )-methylsulfonylethoxy-2-carbomethoxyaminobenzimidazole;

5(6)-ethylthioethoxy-2-carbomethoxyaminobenzimidazole; I 1

5(6)-ethylsulfinylethoxy-2-carbomethoxyaminobenzimidazole;

5(6)-(p-chlorophenylthiomethylsulfinyl)-2-carbomethoxyaminobenzimidazole;and5(6)-(pchlorophenylsulfinylmethylthio)-2-carbomethoxyaminobenzimidazole;

( 6 phen-ylthioethyIthiO-Q-CarbOmethOXyaminobnzimidazole; I

5(6')'-phenylsulfinylethylthio-Q-Carboniethoxyaminobenzimidazole;

5 6 )-phenoxypropylthio-2-carbomethoxyaminobenzimidazole;

5 6 )-phenoxypropylsulfinyl-2-carbomethoxyaminobenzimidazole;

5 (6 )-benzyloxyethylthio-2-carbomethoxyaminobenzimidazole;

5 6 )-benzyloxyethylsulfinyl-2-carbomethoxyaminobenzimidazole;

5 6 )-(t-butoxyethylthio )-2-carbomethoxyaminobenzimidazole;

5 6 t-butoxyethylsulfinyl )-2-carbomethoxyaminobenzimidazole;

5 6 )-phenoxybutylthio-2-carbometh0xyaminobenzimidazole;

5(6)-(2,Z-dimethoxyethylsulfinyl)-2-carbomethoxyaminobenzimidazole;

5 (6 3-methoxypropylsulfinyl)-2-carbomethoxyaminobenzimidazole;

5(6)-benzyloxyethoxy-2-carbomethoxyaminobenzimidazole;

5 6 )-phenoxypropoxy-Z-carbomethoxyaminobenzimidazole;

5(6)-phenoxybutoxy-Z-carbomethoxyaminobenzimidazole;

5(6)-(p-chlorophenoxyethoxy)-2-carbomethoxyaminobenzimidazole;

5 6 p-methoxyphenoxyethoxy )-2-carbomethoxyaminobenzimidazole;

5(6)-(p-methylphenoxyethoxy)-2-carbomethoxyaminobenzimidazole;

5 6 2-methoxy )ethoxy-ethoxy]-2-carbomethoxyaminobenzimidazole;

5(6)-phenoxymethoxy-2-carbomethoxyaminobenzimidazole;

5(6)-benzyloxymethoxy-Z-carbomethoxyaminobenzimidazole;

5(6)-phenylthiomethoxy-2-carbomcthoxyaminobenzimidazole;

5(6 )-phenylsulfinylmethoxy-Z-carbomethoxyaminobenzimidazole;

5 6 )-phenylsulfinylethoxy-2-carbomethoxyaminobenzimidazole;

5(6)-(p-methylbenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole;

5(6)-(p-chlorobenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole;

5(6)-(p-methoxybenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole;

5 6 )-phenoxymethylthio-2carbomethoxyaminoben- 'zimidazole;

5(6)-benzyloxymethylthio-2-carbomethoxyaminobenzimidazole;

5(6)-phenylthiomethylthio-Z-carbomethoxyaminobenzimidazole;

5(6)-phenylsulfonylethoxy-2-carbomethoxyaminobenzimidazole;'

5 6 )-benzyloxyethylthio-2-carbomethoxyaminobenzimidazole;

5 6 )-phenoxymethylsulfinyl-Z-carbomethoxyaminobenzimidaiolcy l 5 6)-benzyloxymethylsulfinyl-2-carbomethoxyam-inobenzimidazole;

20 5(6)-phenylthiomethylsulfinyl-2-carbomethoxyaminobenzimidazole;

5 6 )-phenylsulfinylmethylsulfinyl-Z-carbomethoxyaminobenzimidazole;5(6)-(4-chlorobutylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-(diphenylmethoxyethylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-[2-(4-methylthiophenoxy)ethoxy]-2-carbomethoxyaminobenzimidazole;5(6)-[2-(4-methylsulfinylphenoxy)ethoxy1-2-carbomethoxyaminobenzimidazol,5(6)-[2-(4-methylsulfonylphenoxy)eth0xy]-2-carbomethoxyaminobenzimidazole;5 6 2-( 4-methylthiobenzyloxy )ethoxy -2-carbomethoxyaminobenzimidazole;5(6)-[2-(4-methylsulfinylbenzyloxy)eth0xy1-2-carbomethoxyaminobenzimidazole;

5 6 2-( 4-methylsulfonylbenzyloxy )ethoxy'2-carbomethoxyaminobenzimidazole;

2. The compound of claim 1 wherein said compound is5(6)-[Z-(benzyloxy)ethoxy]-2-carbomethoxyaminobenzimidazole.

3. The compound of claim 1 wherein said compound is5(6)-(3-chloroprop-l-ylsulfinyl)-2-carbomethoxyaminobenzimidazole.

4. The compound of claim 1 wherein said compound is5(6)-[2-(p-chlorophenoxy)ethoxy]-2-carbomethoxyaminobenzimidazole.

5. The compound of claim 1 wherein said compound is5(6)-[Z-(p-methylphenoxy)ethoxy]-2-carbomethoxyaminobenzimidazole.

6. The compound of claim 1 wherein said compound is5(6)-[2-(p-methoxyphenoxy)ethoxy]-2-carbomethoxyaminobenzimidazole.

7. The compound of claim 1 wherein said compound is 5(6)-(but-3-en-l-ylthio)-2-carbomethoxyaminobenzimidazole.

8. A compound selected from the group of compounds represented by theformula:

, N R1 \CCOOR 4 N l H C NCOOR (III) 3 ,929,824 21 22 where R is loweralkyl having 1 to 4 carbon atoms; R or lower alkylsulfonyl substituents;theR moiety being is O(CH ),,O where n is l to 4 and the phenyl ring ofat the 5(6)-p0sition; or a pharmaceutically acoeptable said R moiety ismono-substituted with halo, lower salt thereof. 1 alkyl, lower alkoxy,lower alkylthio, lower alkylsulfinyl, 5

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No.3,929,824 Dated December 30, 1975 Inventofls) COLIN C. BEARD et a1 It iscertified that error appears in the above-identified patent and thatsaid Letters Patent are hereby corrected as shown below:

Column 2, line 11, "methoxyl, should read methoxy, Column 6 line 31, "5(6 should read 5 (6). Column 10, line 29, "118" should read 188 Column10, line 60, "paragrpah" should read paragraph Column 12, line 3, "from"should read for Column 20, line 21, after add or apharmaceuticallyacceptable salt thereof. Claim 8, in the second linebelow the structural formula, "6" should read Claim 9 in the second linebelow the structural formula, "9" should read Signed and Sealed thisfifteenth Day Of June1976 [SEAL] Arrest:

RUTH C. MASON C. MARSHALL DANN Arresting Officer (nmmissjmmr of Parentsand Trademark:

1. A compound selected from the group consisting of:5(6)-(3-chloropropylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-(3-bromopropylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-(3-hydroxypropylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-(2,2-dichloroethylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-(3-phenyl-prop-2-en-1-ylthio)-2-carbomethoxyaminobenzimidazole;5(6)-(3-phenyl-prop-2-en-1-ylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-(3-chloro-prop-2-en-1-ylthio)-2-carbomethoxyaminobenzimidazole;5(6)-(3-chloro-prop-2-en-1-ylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-(2,3-dichloro-prop-2-en-1-ylthio)-2-carbomethoxyaminobenzimidazole;5(6)-(2,3-dichloro-prop-2-en-1-ylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-(2-chloro-prop-2-en-1-ylthio)-2-carbomethoxyaminobenzimidazole;5(6)-(2-chloro-prop-2-en-1-ylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-(but-3-en-1-ylthio)-2-carbomethoxyaminobenzimidazole;5(6)-(but-3-en-1-ylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-(3-phenyl-prop-2-en-1-yloxy)-2-carbomethoxyaminobenzimidazole;5(6)-phenylthioethoxy-2-carbomethoxyaminobenzimidazole;5(6)-phenpropylthio-2-carbomethoxyaminobenzimidazole;5(6)-phenpropylsulfinyl-2-carbomethoxyaminobenzimidazole;5(6)-phenethoxy-2-carbomethoxyaminobenzimidazole;5(6)-phenpropoxy-2-carbomethoxyaminobenzimidazole;5(6)-(prop-2-en-1-yloxy)-2-carbomethoxyaminobenzimidazole;5(6)-ethylsulfinylethylthio-2-carbomethoxyaminobenzimidazole;5(6)-methylthioethylsulfinyl-2-carbomethoxyaminobenzimidazole and5(6)-methylsulfinylethylthio-2-carbomethoxyaminobenzimidazole;5(6)-ethylsulfinylethylsulfinyl-2-carbomethoxyaminobenzimidazole;5(6)-methylsulfonylethoxy-2-carbomethoxyaminobenzimidazole;5(6)-ethylthioethoxy-2-carbomethoxyaminobenzimidazole;5(6)-ethylsulfinylethoxy-2-carbomethoxyaminobenzimidazole;5(6)-(p-chlorophenylthiomethylsulfinyl)-2-carbomethoxyaminobenzimidazole;and5(6)-(p-chlorophenylsulfinylmethylthio)-2-carbomethoxyaminobenzimidazole;5(6)-phenylthioethylthio-2-carbomethoxyaminobenzimidazole;5(6)-phenylsulfinylethylthio-2-carbomethoxyaminobenzimidazole;5(6)-phenoxypropylthio-2-carbomethoxyaminobenzimidazole;5(6)-phenoxypropylsulfinyl-2-carbomethoxyaminobenzimidazole;5(6)-benzyloxyethylthio-2-carbomethoxyaminobenzimidazole;5(6)-benzyloxyethylsulfinyl-2-carbomethoxyaminobenzimidazole;5(6)-(t-butoxyethylthio)-2-carbomethoxyaminobenzimidazole;5(6)-(t-butoxyethylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-phenoxybutylthio-2-carbomethoxyaminobenzimidazole;5(6)-(2,2-dimethoxyethylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-(3-methoxypropylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-benzyloxyethoxy-2-carbomethoxyaminobenzimidazole;5(6)-phenoxypropoxy-2-carbomethoxyaminobenzimidazole;5(6)-phenoxybutoxy-2-carbomethoxyaminobenzimidazole;5(6)-(p-chlorophenoxyethoxy)-2-carbomethoxyaminobenzimidazole;5(6)-(p-methoxyphenoxyethoxy)-2-carbomethoxyaminobenzimidazole;5(6)-(p-methylphenoxyethoxy)-2-carbomethoxyaminobenzimidazole;5(6)-((2-methoxy)ethoxy-ethoxy)-2-carbomethoxyaminobenzimidazole;5(6)-phenoxymethoxy-2-carbomethoxyaminobenzimidazole;5(6)-benzyloxymethoxy-2-carbomethoxyaminobenzimidazole;5(6)-phenylthiomethoxy-2-carbomethoxyaminObenzimidazole;5(6)-phenylsulfinylmethoxy-2-carbomethoxyaminobenzimidazole;5(6)-phenylsulfinylethoxy-2-carbomethoxyaminobenzimidazole;5(6)-(p-methylbenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole;5(6)-(p-chlorobenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole;5(6)-(p-methoxybenzyloxyethoxy)-2-carbomethoxyaminobenzimidazole;5(6)-phenoxymethylthio-2-carbomethoxyaminobenzimidazole;5(6)-benzyloxymethylthio-2-carbomethoxyaminobenzimidazole;5(6)-phenylthiomethylthio-2-carbomethoxyaminobenzimidazole;5(6)-phenylsulfonylethoxy-2-carbomethoxyaminobenzimidazole;5(6)-benzyloxyethylthio-2-carbomethoxyaminobenzimidazole;5(6)-phenoxymethylsulfinyl-2-carbomethoxyaminobenzimidazole;5(6)-benzyloxymethylsulfinyl-2-carbomethoxyaminobenzimidazole;5(6)-phenylthiomethylsulfinyl-2-carbomethoxyaminobenzimidazole;5(6)-phenylsulfinylmethylsulfinyl-2-carbomethoxyaminobenzimidazole;5(6)-(4-chlorobutylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-(diphenylmethoxyethylsulfinyl)-2-carbomethoxyaminobenzimidazole;5(6)-(2-(4-methylthiophenoxy)ethoxy)-2-carbomethoxyaminobenzimidazole;5(6)-(2-(4-methylsulfinylphenoxy)ethoxy)-2-carbomethoxyaminobenzimidazol,5(6)-(2-(4-methylsulfonylphenoxy)ethoxy)-2-carbomethoxyaminobenzimidazole;5(6)-(2-(4-methylthiobenzyloxy)ethoxy)-2-carbomethoxyaminobenzimidazole;5(6)-(2-(4-methylsulfinylbenzyloxy)ethoxy)-2-carbomethoxyaminobenzimidazole;5(6)-(2-(4-methylsulfonylbenzyloxy)ethoxy)-2-carbomethoxyaminobenzimidazole;2. THE COMPOUND OF CLAIM 1 WHEREIN SAID COMPOUND IS5(6)-(2-(BENZYLOXY)ETHOXY)-2-CARBOMETHYOXAMINOBENZIMIDAZOLE.
 3. THECOMPOUND OF CLAIM 1 WHEREIN SAID COMPOUND IS5(6)-(3-CHLOROPROP-1-YLSULFINYL)-2-CARBOMETHOXYMINOBENZIMIDAZOLE.
 4. THECOMPOUND OF CLAIM 1 WHEREIN SAID COMPOUND IS5(6)-((2-(P-CHLOROPHENOXY)ETHOXY)-2-CARBOMETHOXYAMINOBENZIMIDAZOLE. 5.The compound of claim 1 wherein said compound is5(6)-(2-(p-methylphenoxy)ethoxy)-2-carbomethoxyaminobenzimidazole. 6.The compound of claim 1 wherein said compound is5(6)-(2-(p-methoxyphenoxy)ethoxy)-2-carbomethoxyaminobenzimidazole. 7.THE COMPOUND OF CLAIM 1 WHEREIN SAID COMPOUND IS5(6)-(BUT-3-EN-1-YLTHIO)-2-CARBOMETHOXYAMINOBENZIMIDAZOLE.
 8. A compoundselected from the group of compounds represented by the formula:
 9. Acompound selected from the group of compounds represented by theformula: